Phase 1 Study in Patients with Advanced Systemic Mastocytosis
Research type
Research Study
Full title
A Phase 1 Study of BLU-285 in Patients with Advanced Systemic Mastocytosis (advSM) and Relapsed or Refractory Myeloid Malignancies.
IRAS ID
186887
Contact name
Deepti Radia
Contact email
Sponsor organisation
Blueprint Medicines Corporation
Eudract number
2015-001661-12
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 9 months, 1 days
Research summary
Research Summary
This research study is designed to obtain information on the maximum tolerated dose or a lower recommended phase 2 dose, as well as the safety and tolerability of an experimental drug called BLU-285 when given to the following individuals:
1) Patients with Advanced Systemic Mastocytosis (AdvSM), (a disorder where clusters of a certain type of cell in the immune system known as mast cells build up in the bone marrow and/or in tissues) or to
2) Patients with relapsed or refractory myeloid malignancy (a group of diseases or disorders in the myeloid tissue, a type of tissue found in the bone marrow, the spongy inner part of the bone that is responsible for producing the various kinds of blood cells).This is a study involving two parts: 1) A dose-finding part to find the most effective dose amount of the study drug with the least side effects, and 2) An expansion part to confirm if the chosen dose of the study drug is safe and well tolerated.
BLU-285 operates by interfering with certain types of cell changes that are found in many cases of adv SM and some myeloid malignancies. BLU-285 is a capsule that is taken orally once a day for 28 days of a 28-day cycle.
Participants who are eligible for the study will undergo blood and urine sample collection, vital signs measurement, ECG monitoring, disease response assessment by magnetic resonance imaging (MRI) or computed tomography (CT), bone marrow biopsy and adverse event collection.
Approximately 60 adult patients (≥ 18 years of age) will be enroled in the study, which will be conducted at study centres in Europe and the US. Patients will participate in the study for a minimum of approximately 4 months and the expected duration of the study is approximately 33 months.
This study is sponsored by Blueprint Medicines Corporation.
Summary of results
The open-label, phase I EXPLORER trial evaluated the safety, pharmacokinetics, efficacy, and patient-reported outcomes of treatment with avapritinib in 86 patients with systemic mastocytosis, including 69 with advanced systemic mastocytosis.
In the study, the researchers evaluated the effects of avapritinib doses between 30 mg and 400 mg once daily to identify the highest dose that patients could tolerate without experiencing severe side effects. The safety of avapritinib was also assessed.
The adverse events most frequently reported during treatment included swelling around the eyes, anemia, diarrhea, nausea, fatigue, swelling in the limbs, and low platelet count.
The overall response rate (ORR) was 77% in 57 patients that could be evaluated. Additionally, the complete remission rate was 40%. Treatment with avapritinib was associated with reductions of 50% or more in the number of abnormal cells in the bone marrow in 94% of patients, as well as in the levels of a specific protein called serum tryptase in 99% of patients. Patients who received avapritinib reported improvements in their quality of life and overall well-being.
The overall study results leading to the approval of avapritinib in the select indications are available publicly.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
15/SC/0685
Date of REC Opinion
14 Dec 2015
REC opinion
Further Information Favourable Opinion